The Complex Association of Daily Opioid Dose with Visits for Pain in Sickle Cell Disease: Tolerance or Treatment-Refractory Pain?

Abstract Introduction Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given the risks of high opioid doses and high hospital utilization. A prior study by our group suggested that outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. The present larger naturalistic observational study was undertaken to determine whether the results were reliable across multiple acute care settings. Methods One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, visits to the infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models that were controlled for patient, disease, and treatment characteristics. Results Outpatient opioid dosage predicted dosage during visits but did not predict visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses, this relationship was nonlinear, with a clear positive association only for those prescribed the lowest 50% of dosages. Discussion Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, which is more consistent with opioid tolerance than with treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, which suggests that opioid consumption at lower levels is driven by intermittent acute pain and opioid consumption at higher levels is driven by chronic pain.